Elevated sclerostin levels contribute to reduced bone mineral density in non-ambulatory stroke patients

Osteoporosis following stroke is a significant impediment to patient recovery. Decreased mechanical loading and locomotion following the onset of paralysis in stroke patients, especially those who are non-ambulatory, contributes greatly to bone loss. Sclerostin, a protein encoded by the SOST gene, a...

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Main Authors: Hye Kyoung Lee, Geneva Rose Notario, Sun Young Won, Jung Hwan Kim, Su Min Lee, Ha Seong Kim, Sung-Rae Cho
Format: Article
Language:English
Published: Elsevier 2025-06-01
Series:Bone Reports
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Online Access:http://www.sciencedirect.com/science/article/pii/S2352187225000063
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author Hye Kyoung Lee
Geneva Rose Notario
Sun Young Won
Jung Hwan Kim
Su Min Lee
Ha Seong Kim
Sung-Rae Cho
author_facet Hye Kyoung Lee
Geneva Rose Notario
Sun Young Won
Jung Hwan Kim
Su Min Lee
Ha Seong Kim
Sung-Rae Cho
author_sort Hye Kyoung Lee
collection DOAJ
description Osteoporosis following stroke is a significant impediment to patient recovery. Decreased mechanical loading and locomotion following the onset of paralysis in stroke patients, especially those who are non-ambulatory, contributes greatly to bone loss. Sclerostin, a protein encoded by the SOST gene, accumulates as a result of reduced mechanical loading and inhibits bone formation. This study explores the relationship between mechanical unloading, sclerostin levels, and bone mineral density (BMD) in stroke patients, utilizing three cohorts. Analysis of Cohort 1, consisting of patients with available sclerostin level measurements, found significantly elevated sclerostin levels in non-ambulatory patients compared to ambulatory patients, indicating the influence of ambulatory status on sclerostin regulation. Cohort 2, consisting of patients with BMD measurements, demonstrated that prolonged mechanical unloading in non-ambulatory patients resulted in a greater decline in BMD over time. Analysis in Cohort 3 patients, who had bilateral BMD measurements available, revealed that hemiplegic sides subjected to reduced mechanical loading exhibited lower BMD compared to non-hemiplegic sides. These findings collectively confirm the hypothesis that reduced mechanical loading elevates sclerostin levels and accelerates bone loss. By integrating data across the three cohorts, this study underscores the critical impact of mechanical unloading on bone health, particularly in chronic stroke patients with limited mobility. Our study provides clinical insights for treatments integrating ambulatory status, sclerostin levels, and BMD in chronic stroke patients and highlights an increased need for therapeutics targeting mechanical loading pathways and sclerostin accumulation which can be administered to treat chronic osteoporosis following stroke.
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spelling doaj-art-656d976a6c3646bf904e1402348a8a132025-08-20T02:39:33ZengElsevierBone Reports2352-18722025-06-012510182910.1016/j.bonr.2025.101829Elevated sclerostin levels contribute to reduced bone mineral density in non-ambulatory stroke patientsHye Kyoung Lee0Geneva Rose Notario1Sun Young Won2Jung Hwan Kim3Su Min Lee4Ha Seong Kim5Sung-Rae Cho6Department of Rehabilitation Medicine, Yonsei University College of Medicine, Seoul, Republic of Korea; Research Institute of Rehabilitation Medicine, Yonsei University College of Medicine, Seoul, Republic of Korea; Graduate Program of Biomedical Engineering, Yonsei University College of Medicine, Seoul, Republic of Korea; Department of Medicine, Yonsei University College of Medicine, Seoul, Republic of KoreaDepartment of Rehabilitation Medicine, Yonsei University College of Medicine, Seoul, Republic of Korea; Research Institute of Rehabilitation Medicine, Yonsei University College of Medicine, Seoul, Republic of Korea; Graduate School of Medical Science, Brain Korea 21 Project, Yonsei University College of Medicine, Seoul, Republic of KoreaDepartment of Rehabilitation Medicine, Yonsei University College of Medicine, Seoul, Republic of Korea; Research Institute of Rehabilitation Medicine, Yonsei University College of Medicine, Seoul, Republic of Korea; Department of Medicine, Yonsei University College of Medicine, Seoul, Republic of KoreaDepartment of Rehabilitation Medicine, Yonsei University College of Medicine, Seoul, Republic of Korea; Department of Medicine, Yonsei University College of Medicine, Seoul, Republic of KoreaDepartment of Rehabilitation Medicine, Yonsei University College of Medicine, Seoul, Republic of Korea; Department of Nursing, Yonsei University College of Nursing, Seoul, Republic of KoreaDepartment of Medicine, Yonsei University College of Medicine, Seoul, Republic of Korea; Seosong Hospital, Incheon, Republic of Korea.Department of Rehabilitation Medicine, Yonsei University College of Medicine, Seoul, Republic of Korea; Research Institute of Rehabilitation Medicine, Yonsei University College of Medicine, Seoul, Republic of Korea; Graduate Program of Biomedical Engineering, Yonsei University College of Medicine, Seoul, Republic of Korea; Graduate School of Medical Science, Brain Korea 21 Project, Yonsei University College of Medicine, Seoul, Republic of Korea; Rehabilitation Institute of Neuromuscular Disease, Yonsei University College of Medicine, Seoul, Republic of Korea; Brain Research Institute, Yonsei University College of Medicine, Seoul, Republic of Korea; Corresponding author at: Department and Research Institute of Rehabilitation Medicine, Yonsei University College of Medicine, 50-1 Yonsei-ro, Seodaemun-gu, Seoul 03722, Republic of Korea.Osteoporosis following stroke is a significant impediment to patient recovery. Decreased mechanical loading and locomotion following the onset of paralysis in stroke patients, especially those who are non-ambulatory, contributes greatly to bone loss. Sclerostin, a protein encoded by the SOST gene, accumulates as a result of reduced mechanical loading and inhibits bone formation. This study explores the relationship between mechanical unloading, sclerostin levels, and bone mineral density (BMD) in stroke patients, utilizing three cohorts. Analysis of Cohort 1, consisting of patients with available sclerostin level measurements, found significantly elevated sclerostin levels in non-ambulatory patients compared to ambulatory patients, indicating the influence of ambulatory status on sclerostin regulation. Cohort 2, consisting of patients with BMD measurements, demonstrated that prolonged mechanical unloading in non-ambulatory patients resulted in a greater decline in BMD over time. Analysis in Cohort 3 patients, who had bilateral BMD measurements available, revealed that hemiplegic sides subjected to reduced mechanical loading exhibited lower BMD compared to non-hemiplegic sides. These findings collectively confirm the hypothesis that reduced mechanical loading elevates sclerostin levels and accelerates bone loss. By integrating data across the three cohorts, this study underscores the critical impact of mechanical unloading on bone health, particularly in chronic stroke patients with limited mobility. Our study provides clinical insights for treatments integrating ambulatory status, sclerostin levels, and BMD in chronic stroke patients and highlights an increased need for therapeutics targeting mechanical loading pathways and sclerostin accumulation which can be administered to treat chronic osteoporosis following stroke.http://www.sciencedirect.com/science/article/pii/S2352187225000063StrokeBone mineral densitySclerostinAmbulatory statusMechanical loading
spellingShingle Hye Kyoung Lee
Geneva Rose Notario
Sun Young Won
Jung Hwan Kim
Su Min Lee
Ha Seong Kim
Sung-Rae Cho
Elevated sclerostin levels contribute to reduced bone mineral density in non-ambulatory stroke patients
Bone Reports
Stroke
Bone mineral density
Sclerostin
Ambulatory status
Mechanical loading
title Elevated sclerostin levels contribute to reduced bone mineral density in non-ambulatory stroke patients
title_full Elevated sclerostin levels contribute to reduced bone mineral density in non-ambulatory stroke patients
title_fullStr Elevated sclerostin levels contribute to reduced bone mineral density in non-ambulatory stroke patients
title_full_unstemmed Elevated sclerostin levels contribute to reduced bone mineral density in non-ambulatory stroke patients
title_short Elevated sclerostin levels contribute to reduced bone mineral density in non-ambulatory stroke patients
title_sort elevated sclerostin levels contribute to reduced bone mineral density in non ambulatory stroke patients
topic Stroke
Bone mineral density
Sclerostin
Ambulatory status
Mechanical loading
url http://www.sciencedirect.com/science/article/pii/S2352187225000063
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